Prenatal interventions for fetal growth restriction in animal models: A systematic review

Valenzuela, Ignacio; Kinoshita, Mari; Merwe, Johannes van der; Maršál, Karel; Deprest, Jan

doi:10.1016/j.placenta.2022.06.007

Cited by 12 publications

(7 citation statements)

References 218 publications

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“…The most popular animal species used in research are mice and rats (79%) and sheep (16%). The remainder includes guinea pigs, rabbits, chickens, pigs, nonhuman primates, and other species [ 26 ].…”

Section: Animal Models Of Fgrmentioning

confidence: 99%

Molecular Pathways of Altered Brain Development in Fetuses Exposed to Hypoxia

Orzeł

Unrug-Bielawska

Filipecka-Tyczka

et al. 2023

IJMS

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Perinatal hypoxia is a major cause of neurodevelopmental impairment and subsequent motor and cognitive dysfunctions; it is associated with fetal growth restriction and uteroplacental dysfunction during pregnancy. This review aims to present the current knowledge on brain development resulting from perinatal asphyxia, including the causes, symptoms, and means of predicting the degree of brain damage. Furthermore, this review discusses the specificity of brain development in the growth-restricted fetus and how it is replicated and studied in animal models. Finally, this review aims at identifying the least understood and missing molecular pathways of abnormal brain development, especially with respect to potential treatment intervention.

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Section: Animal Models Of Fgrmentioning

confidence: 99%

Molecular Pathways of Altered Brain Development in Fetuses Exposed to Hypoxia

Orzeł

Unrug-Bielawska

Filipecka-Tyczka

et al. 2023

IJMS

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“…There are multiple animal models of placental insufficiency, chronic fetal hypoxia and/or FGR, utilising small and large animal experimental designs ( 19 , 20 ). A recent systematic review reports that mice and rats were the most used animals for intervention studies in FGR (79%) followed by sheep (16%) ( 21 ). The clinical complexity and heterogeneous nature of human FGR means that no single animal model will perfectly mimic the human condition.…”

Section: Introductionmentioning

confidence: 99%

Phenotype of early-onset fetal growth restriction in sheep

Sutherland,

White,

Rock

et al. 2024

Front. Endocrinol.

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IntroductionFetal growth restriction (FGR) is a common pregnancy complication, caused by placental insufficiency, with serious adverse consequences for development in utero and postnatal wellbeing. There are no antenatal treatments to improve growth or organ development in FGR, and animal models are essential to mimic the physiological adaptations in FGR and to assess potential interventions. This study aimed to identify the temporal nature of reduced developmental trajectory in fetuses with FGR, and to examine the effects of common factors that may mediate differential growth such as glucocorticoid treatment. We hypothesised that the trajectory of growth would be adversely impacted by FGR.MethodsFGR was induced via surgical placental insufficiency in fetal sheep (89 days gestation/0.6 gestation; n=135) and compared to age-matched controls over the last third of gestation and into neonatal life (n=153).ResultsBody weight of FGR fetuses/lambs was significantly reduced compared to controls (p<0.0001) from 127 days of gestation (term is 148 days), with increased brain:body weight ratio (p<0.0001) indicative of brain sparing. All biometric measures of body size were reduced in the FGR group with the exception of biparietal (head) diameter. The trajectory of body growth in the last trimester of sheep pregnancy was significantly reduced in the FGR group compared to controls, and stillbirth rate increased with longer gestation.DiscussionThis work provides a well characterised FGR animal model that mimics the known physiological adaptations in human pregnancy and can be used to determine the efficacy of potential interventions.

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“…Several animal models have been used to mimic human FGR and its consequences 16 . Animal models enable researchers to overcome the evident ethical constrains in studying human subjects, while allowing to control variables to limit noise and bias.…”

Section: Introductionmentioning

confidence: 99%

“…Neurogenesis onset occurs in the first trimester in the rabbit brain, and white matter maturation is a perinatal process that continues throughout the first year of life in both the human and rabbit, unlike the more precocial sheep and more altricial mouse and rat 19 , 20 . These practical considerations make the rabbit a valuable translational model to study the short and long-term effects of prenatal conditions and, eventually, test perinatal interventions 16 .…”

Section: Introductionmentioning

confidence: 99%

Long-term pulmonary and neurodevelopmental impairment in a fetal growth restriction rabbit model

Valenzuela,

Regin,

Gie

et al. 2023

Sci Rep

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Fetal growth restriction (FGR) remains one of the main obstetrical problems worldwide, with consequences beyond perinatal life. Animal models with developmental and structural similarities to the human are essential to understand FGR long-term consequences and design novel therapeutic strategies aimed at preventing or ameliorating them. Herein, we described the long-term consequences of FGR in pulmonary function, structure, and gene expression, and characterized neurodevelopmental sequelae up to preadolescence in a rabbit model. FGR was induced at gestational day 25 by surgically reducing placental blood supply in one uterine horn, leaving the contralateral horn as internal control. Neonatal rabbits born near term were assigned to foster care in mixed groups until postnatal day (PND) 21. At that time, one group underwent pulmonary biomechanical testing followed by lung morphometry and gene expression analysis. A second group underwent longitudinal neurobehavioral assessment until PND 60 followed by brain harvesting for multiregional oligodendrocyte and microglia quantification. FGR was associated with impaired pulmonary function and lung development at PND 21. FGR rabbits had higher respiratory resistance and altered parenchymal biomechanical properties in the lungs. FGR lungs presented thicker alveolar septal walls and reduced alveolar space. Furthermore, the airway smooth muscle content was increased, and the tunica media of the intra-acinar pulmonary arteries was thicker. In addition, FGR was associated with anxiety-like behavior, impaired memory and attention, and lower oligodendrocyte proportion in the frontal cortex and white matter. In conclusion, we documented and characterized the detrimental pulmonary function and structural changes after FGR, independent of prematurity, and beyond the neonatal period for the first time in the rabbit model, and describe the oligodendrocyte alteration in pre-adolescent rabbit brains. This characterization will allow researchers to develop and test therapies to treat FGR and prevent its sequelae.

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Prenatal interventions for fetal growth restriction in animal models: A systematic review

Cited by 12 publications

References 218 publications

Molecular Pathways of Altered Brain Development in Fetuses Exposed to Hypoxia

Molecular Pathways of Altered Brain Development in Fetuses Exposed to Hypoxia

Phenotype of early-onset fetal growth restriction in sheep

Long-term pulmonary and neurodevelopmental impairment in a fetal growth restriction rabbit model

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